A continuation of investigations on the regulation of enzyme activities and the rates of synthesis and degradation of cholesterol, bile acid and fatty acid synthesizing enzymes and on the rates of synthesis of serum lipoproteins is proposed. In these studies attempts will be made to determine the mechanism whereby insulin and glucagon bring about a change in beta-hydroxy-beta-methylglutaryl coenzyme A reductase activity. These investigations will attempt to determine whether changes in activity are due to changes in quantity of this enzyme or to changes in activity of preexisting enzyme. Studies on cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme of bile acid synthesis, will concentrate largely on attempts to purify this enzyme to homogeneity. Subsequent studies will attempt to determine the mechanism by which hormones regulate the activity of this enzyme. Studies on the regulation of the rates of synthesis of serum lipoproteins will be attempted once the major apoprotein of each lipoprotein is purified and monospecific antisera to each protein is prepared. Investigations on acetyl-CoA carboxylase will attempt to identify the mechanism whereby glucagon and insulin modify the activity of this enzyme in short-term incubations with isolated hepatocytes. Studies on the fatty acid synthetase will concentrate on the purification of mRNA for this enzyme and its translation in a cell-free protein synthesizing system. BIBLIOGRAPHIC REFERENCES: Dugan, R.E., and Porter, J.W. (1976) in The Enzymes of Biological Membranes, Anthony Martonosi, Ed., Plenum Publishing Co., Vol. 2, pp. 161-206. Membrane-Bound Enzymes of Sterol Metabolism. Dugan, R.E. and Porter, J.W. (1977) in Biochemical Actions of Hormones, Vol. 4, Gerald Litwack, Ed., Academic Press, Inc., New York. Hormonal Regulation of Cholesterol Synthesis.